| 초록 |
A modern approach to generate new aminoglycoside antibiotics or to improve the production of valuable natural congeners for use in the synthesis of semisynthetic aminoglycosides is through metabolic pathway engineering and/or combinatorial biosynthesis, both require a detailed knowledge of the biosynthetic pathways and the involved enzymes. To better understand aminoglycoside biosynthesis, we have completed, and report herein, the in vitro reconstitution of one of the most important aminoglycoside biosynthesis. Study of the crystal structure of the key enzyme reveals a unique active site conformation helping to explain its substrate specificity. Some of the newly characterized intermediates displayed similar premature termination codon readthrough activity but with reduced toxicity. This study demonstrates that the elucidation of minor biosynthetic pathways can be an alternative strategy to mine for new aminoglycosides which are difficult to access from nature. |
